Schedule H

Intravenous

Formulation Strength Pack Size

IV infusion concentrate 2.5 mg/mL 5 mL vial (12.5 mg total)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

ACUTE DECOMPENSATED HEART FAILURE (Short-term Inotropic Support)

Clinical Context:

• Use restricted to ICU / specialist cardiology settings with haemodynamic monitoring

• Indicated for low cardiac output states despite adequate diuretics and vasodilators

• Particularly useful when beta-blockers cannot be discontinued

Dosing Protocol (IV Infusion):

Parameter Recommendation

Loading dose 6–12 mcg/kg over 10 minutes (OPTIONAL — only if SBP >90 mmHg and low hypotension risk)

Starting dose 0.05 mcg/kg/min continuous IV infusion

Titration Increase by 0.05 mcg/kg/min every 30–60 minutes based on haemodynamic response and tolerability

Usual maintenance dose 0.05–0.2 mcg/kg/min

Maximum dose 0.2 mcg/kg/min

Infusion duration 24 hours (maximum 48 hours)

Key Clinical Notes:

• Omit loading dose if baseline SBP <90 mmHg or high hypotension risk

• Haemodynamic effects persist 7–10 days post-infusion due to active metabolite (OR-1896)

• Continuous ECG and BP monitoring mandatory during infusion

• Ensure normokalemia before and during infusion

Secondary Indications — Adults Only (Off-label)

Indication Dosing Duration Notes Evidence Basis

Advanced heart failure bridge-to-transplant or LVAD Starting: 0.05 mcg/kg/min; Maintenance: 0.05–0.2 mcg/kg/min Single 24–48 hr infusion; may repeat every 2–4 weeks Specialist only — OFF-LABEL Indian advanced HF practice protocols; observational studies

Cardiorenal syndrome (Type 1 with low perfusion) Starting: 0.05 mcg/kg/min; Maintenance: 0.05–0.2 mcg/kg/min 24 hours Specialist only — OFF-LABEL; refractory cases only Limited evidence; Indian tertiary centre practice for renal perfusion improvement

PAEDIATRIC DOSING (Specialist Only)

⚠️ NOT APPROVED for routine paediatric use

Primary Indications (Approved / Standard in India)

Not applicable — No approved paediatric indications in India

Secondary Indications — Paediatric (Off-label)

Paediatric Cardiac Failure / Post-Cardiac Surgery Recovery — OFF-LABEL

Use only under specialist paediatric cardiac ICU supervision

Parameter Recommendation

Loading dose AVOIDED due to hypotension risk

Starting dose 0.05 mcg/kg/min continuous IV infusion

Titration Increase by 0.025–0.05 mcg/kg/min based on response

Usual maintenance dose 0.05–0.2 mcg/kg/min

Maximum dose 0.2 mcg/kg/min

Duration Typically 24 hours

Safety Requirements:

• Continuous haemodynamic and ECG monitoring mandatory

• Frequent electrolyte monitoring (especially potassium)

• Invasive BP monitoring preferred

Age Restriction:

• Not recommended below 1 year of age except under superspecialist supervision in tertiary paediatric cardiac centres

Evidence Basis: Limited observational data; Indian paediatric cardiac ICU practice (AIIMS, tertiary centres)

ESRD / Dialysis Avoid repetitive dosing unless benefits clearly outweigh risks; specialist supervision essential

Note: Active metabolite (OR-1896) has prolonged half-life in renal impairment

• Severe hypotension (SBP <85 mmHg)

• Significant ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation)

• Hypertrophic obstructive cardiomyopathy with dynamic outflow tract obstruction

• Severe aortic or mitral stenosis limiting cardiac output

• Severe uncorrected hypovolaemia

• Severe renal impairment with no ICU monitoring available

• Severe hepatic impairment without specialist supervision

• Known hypersensitivity to levosimendan or excipients

• Pre-existing atrial fibrillation or other atrial arrhythmias

• Moderate hypotension (SBP 85–100 mmHg) — correct before initiating

• Uncorrected hypovolaemia — fluid resuscitation before use

• Concurrent potent vasodilators or beta-blockers

• Prolonged baseline QT interval

• Hypokalaemia or hypomagnesaemia — correct before use

• Elderly and frail patients (higher hypotension sensitivity)

• Torsades de pointes risk factors

• Acute coronary syndrome (may worsen ischaemia in certain situations)

Aspect Details

Safety status Limited human data; potential risk unknown

Risk category Not formally classified under Indian system

When to use Only in life-threatening conditions where benefit clearly outweighs risk; ICU setting mandatory

Preferred alternatives Dobutamine or milrinone under obstetric cardiology guidance

Monitoring required Continuous maternal BP monitoring; fetal heart rate monitoring if used in late pregnancy

Aspect Details

Compatibility Not recommended during breastfeeding

Drug levels in milk Unknown

Preferred alternatives Avoid use in lactating women; if essential, consider temporary cessation of breastfeeding

Infant monitoring Not applicable (use should be avoided)

Aspect Recommendation

Starting dose 0.05 mcg/kg/min (omit loading dose)

Titration Slower titration; increase every 60 minutes rather than 30 minutes

Maximum dose 0.2 mcg/kg/min (often lower doses sufficient)

Extra risks Hypotensive episodes, decline in renal function, arrhythmic events, increased sensitivity to haemodynamic changes

Interacting Drug Effect Management

QT-prolonging agents (amiodarone, sotalol, macrolides, fluoroquinolones, antipsychotics) Additive QT prolongation; increased torsades de pointes risk Avoid combination if possible; if essential, continuous ECG monitoring with QTc assessment

Potent vasodilators (IV nitroglycerin, nitroprusside) Synergistic hypotension; may cause severe BP drop Use with extreme caution; frequent BP monitoring; may need dose reduction of either agent

Loop diuretics (high-dose furosemide) Additive hypotension and hypovolaemia Ensure adequate volume status; monitor BP closely

Interacting Drug Effect Management

Beta-blockers May partially antagonise positive inotropic effects Use cautiously; levosimendan often used specifically in beta-blocked patients — monitor response

Digoxin Possible additive inotropic and chronotropic effects Monitor for tachyarrhythmias; ECG monitoring

Potassium-lowering agents (thiazides, loop diuretics) Increased arrhythmia risk from hypokalaemia Maintain serum potassium >4.0 mEq/L during infusion

CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin) May increase active metabolite exposure Monitor for prolonged effects; no specific dose adjustment established

Antiarrhythmics (Class I, III) Additive effects on cardiac conduction ECG monitoring advised throughout infusion

• Hypotension (dose-related)

• Headache

• Nausea

• Tachycardia or palpitations

• Dizziness

• Insomnia

• Hypokalaemia

Adverse Effect Clinical Action

Atrial fibrillation or ventricular arrhythmias May require rate control, antiarrhythmics, or discontinuation

Torsades de pointes Rare but life-threatening; immediate discontinuation; magnesium, defibrillation if needed

Severe hypotension requiring vasopressor support Reduce infusion rate or stop; initiate vasopressors (norepinephrine)

Myocardial ischaemia Occurs in preload-dependent states; discontinue and reassess

Cardiac arrest Rare; full resuscitation; ICU monitoring mandatory for 24–48 hrs post-infusion

During infusion Continuous ECG, BP monitoring (hourly minimum; invasive preferred), urine output, haemodynamic parameters if available

Post-infusion Monitor for delayed arrhythmias and hypotension for 24–48 hours (active metabolite effect persists)

Long-term Not applicable — drug used for acute short-term support only

Brand Name Manufacturer

Simendan Lupin

Simate La Renon

Simenda Macleods

Levgard Intas

12.5 mg/5 mL vial ₹5,500–7,500 per vial

Notes:

• Not under NLEM price control

• High-cost injectable; typically stocked in ICU/CCU only

• Single vial often sufficient for one 24-hour infusion in average adult

1. Beta-blocker compatibility: Unlike dobutamine, levosimendan provides inotropic support in patients on beta-blockers — a key advantage in acute-on-chronic heart failure

1. Loading dose decision: Omit loading dose in borderline hypotension (SBP 90–100 mmHg), elderly, or hypovolaemic patients to reduce hypotension risk

1. Prolonged effect: Active metabolite (OR-1896) provides haemodynamic benefit for 7–10 days after a single 24-hour infusion — factor this into repeat dosing decisions

1. No tachyphylaxis: Unlike dobutamine, efficacy is maintained over 24–48 hour infusion without dose escalation

1. Potassium vigilance: Correct hypokalaemia before and during infusion — arrhythmia risk significantly increases with low K⁺

1. Post-infusion monitoring: Continue ECG and haemodynamic monitoring for at least 24–48 hours after stopping infusion due to active metabolite accumulation

levosimendan; heart failure; inotrope; inodilator; calcium sensitizer; ICU-use; specialist-only; renal-caution; QT-risk; cardiac-output-support; ADHF

RxIndia v1.0 — 02 May 2025

• CDSCO product listings and approved prescribing information

• National Formulary of India (NFI) 2021

• AIIMS ICU Formulary 2022

• API Textbook of Medicine

• Heart Failure Association of India — Guidelines for Advanced Heart Failure Management

• Indian tertiary centre specialist protocols (AIIMS Delhi, PGI Chandigarh)

• International RCTs (SURVIVE, REVIVE trials) — referenced for off-label use context only